DESCRIPTION: (Applicant's Abstract) The proposed project is a prospective natural history study of early chronic hepatitis C infection in a seroincident cohort of injection drug users (IDUs) between the ages of 18-30. The investigators of this study aim to examine the progression of HCV clinical and virologic markers, while establishing a repository of histological tissue for future immunological inquiries. They also aim to examine factors that potentially influence immediate and long-term response to treatment or course of disease progression by measuring their effects on HCV markers over time. Study participants will consist of approximately 125 IDUs with identified incident or recent HCV infection. Participants will be identified and recruited from an existing cohort of young IDUs enrolled in a CDC-funded prospective study on drug injection and disease transmission. All participants will be interviewed regarding their health status, medical treatment experiences, alcohol and substance use. Serum specimens will be obtained and tested to assess viral activity and liver function. Tests include: serum HCV RNA quantification, viral genotyping, and serum transaminases (ALT, AST). A subsample of incident cases will be used to examine the extent and pace of genetic diversification. All participants will be observed for four years and asked to return every three months for follow-up interviews and serological testing. During the course of the study, all patients will be referred to care at the University of Illinois Medical Center Digestive Disease and Liver Center. Biopsies conducted during normal care will also be used for analysis.